PROJECT SUMMARY/ABSTRACT: We propose the acquisition of a new NovaSeq 6000 ultra high-throughput DNA sequencing instrument. The proposed instrument will be placed in a shared setting at the Stanford Center for Genomics and Personalized Medicine (SCGPM) Genome Sequencing Service Center (GSSC) and operated by a highly trained group of staff experienced with Illumina sequencing and genomic technologies. The SCGPM GSSC is a core facility that was founded in 2009 and is open to the entire Stanford community. Since its inception the SCGPM GSSC has produced sequencing data for over 400 Stanford researchers and more than 90 laboratory groups. The presence of a new NovaSeq 6000 sequencer will greatly increase the sequencing throughput capabilities of the center and shorten turnaround time while dramatically reducing sequencing prices and offer opportunities for the development of new sequencing applications. Several of the instruments that are currently present in the SCGPM GSSC are at the end of their lifetimes (well over four years by the earliest start date of this grant) and cost-benefit analysis favors the purchase of new hardware. The Major and Minor Users highlighted in this proposal range from junior faculty who are just starting their own laboratories to established full professors with over 30 years of research experience. Nearly all of the Users have NIH funding, and their genomics studies depend on affordable and customizable ultra high-throughput, next generation sequencing technologies. We predict that usage of the NovaSeq 6000 instrument will approach maximum capacity due to the large demand and need for cost-effective high throughput sequencing. DNA sequence data collected with the proposed instrument will positively impact a broad cross section of human diseases and disabilities, notably: cardiovascular disease, pulmonary hypertension, type 2 diabetes mellitus, inflammatory bowel diseases, developmental defects, cancer, sleep disorders, obesity, and aging. The research performed in these studies will help pave the way for better interpretations of human genome polymorphisms as well as the translation of new assays and technologies to the clinic. Stanford researchers who perform DNA sequencing assays made possible by this instrument publish very high profile studies, and so we expect this instrument to have a major impact in biomedical research. !